美国处方书写管理制度初探

目的:规范医疗机构的处方书写和调配行为。方法:系统分析美国处方书写管理的相关规定和要求,探讨中、美两国处方书写管理之间的差异。结果与结论:美国处方书写管理规定具有具体、灵活、操作性强和以人为本等特点,我国有必要借鉴其处方书写管理制度,以进一步规范我国医疗机构的处方书写和调配行为。     

p16、Cyclin D1在增生性子宫内膜及子宫内膜癌中的表达

目的 :探讨 p16和 Cyclin D1在内膜癌发生、发展中的作用。方法 :采用免疫组化 S—P法对 12例正常子宫内膜、2 2例增生性子宫内膜及 4 1例子宫内膜癌中 p16和 Cyclin D1表达进行了研究。结果 :在单纯加复合增生、不典型增生及子宫内膜癌中 ,p16表达呈下降趋势 ,内膜癌与正常内膜及增生性内膜有显著性差异 (P<0 .0 1,P <0 .0 5 ) ;而Cyclin D1表达呈上升趋势 ,增生性子宫内膜、子宫内膜癌与正常内膜有显著性差异 (P<0 .0 5 ,P<0 .0 1)。不典型增生与单纯加复合增生 Cyclin D1过表达有显著性差异 (P<0 .0 1)。子宫内膜癌中 ,p16表达随细胞分化程度下降而降低 ,而Cyclin D1则随分化程度下降而上升 ,二者呈负相关。结论 :p16、Cyclin D1异常参与子宫内膜癌的发生 ;p16低表达、Cyclin D1过表达与内膜癌的恶性生物学行为有关 ;Cyclin D1核过表达可能是一个早期分子事件     

Ventilatory response to CO2 at rest and during positive and negative work in normoxia and hyperoxia

Summary Ventilation versus alveolar relationships were determined by the steady-state method in 6 normal male subjects at rest and during positive and negative work at one load in both normoxic and hyperoxic condition. In 5 subjects the slopes of the lines during positive and negative work increased in normoxia as compared with rest. This effect was less evident in hyperoxia. It was also found that the slopes of the lines in positive and in negative work were about the same in both normoxic and hyperoxic conditions. Oxygen uptake and CO₂ production during positive work is higher than during negative work.These results suggest that: 1) the disagreement between various authors on the change of the slope of the line may be due to the differences in the method of calculation of the slope or the method of the determination of lines; 2) the stimuli from the muscle spindles in the working muscle during exercise probably do not contribute to the increase in ventilatory response to CO₂; 3) the increased slope of the normoxic line during exercise may be due to the interaction of several factors such as impulses from working muscles, chemosensitivity of central or peripheral chemoreceptors, adrenal-sympathetic pathways or temperature; 4) respiratory oscillations of or do not seem to influence the respiratory response to CO₂.This study was supported in part by a grant from the Netherlands Organization for the Advancement of Pure Research (Z.W.O.)     

Interaction of CO2 and positive and negative exercise stimuli on the ventilation in man

Ventilatory response curves to CO₂ were determined at rest and during different workloads and pedal rates, of negative and positive exercise in four subjects. It appeared that the slope of only the lower part of the curvilinear ventilatory response curve to CO₂ (at low stimuli) shows a significant positive correlation with the metabolism, independent of the type of excercise, force or speed of muscle contraction. The slope of the higher part was only determined by the CO₂ stimulus. An interaction of low CO₂ stimuli with an unknown exercise-stimulus is suggested, which results in a response of the ventilation to CO₂, proportional to the metabolism.     

Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes

The influence of diabetes mellitus on brain pathology is increasingly recognized. Previous contributions of our laboratory demonstrated in models of type 1 diabetes (nonobese diabetic and streptozotocin (STZ)-treated mice), a marked astrogliosis and neurogenesis deficit in hippocampus and increased expression of hypothalamic neuropeptides. In the present investigation, we further analyzed alterations of astroglia and neurons in the hippocampus of mice 1 month after STZ-induced diabetes. Results showed that these STZ-diabetic mice presented: (a) increased number of astrocytes positive for apolipoprotein-E (Apo-E), a marker of ongoing neuronal dysfunction; (b) abnormal expression of early gene products associated with neuronal activation, including a high number of Jun + neurons in CA1 and CA3 layers and dentate gyrus, and of Fos-expressing neurons in CA3 layer; (c) augmented activity of NADPH-diaphorase, linked to oxidative stress, in CA3 region. These data support the concept that uncontrolled diabetes leads to hippocampal pathology, which adjoin to changes in other brain structures such as hypothalamus and cerebral cortex.     

Buffering and H+ ion dynamics in muscle tissues

After anaerobic activity with release of large quantities of intermediary metabolic end products, further energy production critically depends on rapid elimination of H+ ions from the muscle tissues to secure key enzymatic activities. The involved processes, interactions and interrelationships of mechanisms have been analyzed on the basis of a physiological model and available experimental data. The H+ elimination from muscle tissue is a multifactorial process primarily governed by the capillary H+ transport capacitance, effected by buffering capabilities of intracellular and capillary fluids compartments, by dynamically interrelated regulation of intracellular and extracellular pH, by the magnitude and quality of convective perfusional transfer and further factors. Model calculations strongly resemble experimental data obtained in isolated perfused muscles and suggest that discrepancies between disparate literature data are attributable to experimental limitations.     

Reduced expression of the global regulator protein CsrA in Legionella pneumophila affects virulence-associated regulators and growth in Acanthamoeba castellanii

Legionella bacteria have a developmental cycle in which they go from existing in the aquatic environment to replicating inside eukaryotic host cells. The adaptation to the new environment requires an efficient regulatory system. Overexpression of CsrA, a global regulatory protein found in a variety of gram-negative bacteria has been shown to suppress virulence-associated traits in Legionella pneumophila. Since evidence resulting only from overproduction may not be sufficient to validate the role of a regulatory protein, a csrA mutant strain, CsrA(-), with a drastically reduced production of CsrA, was created. Using RNA slot blots and Western blotting it was shown that fliA and flaA, genes which contribute to flagellation, were expressed early in the mutant. Additionally, in CsrA(-) the levels of the stationary-phase sigma factor, RpoS, and a recently described regulator of virulence traits, LetE, were increased. Growth curves of CsrA(-) bacteria were delayed with pigment production occurring at the same OD578 but at reduced levels in the mutant. Replication ability of the CsrA(-) mutant in amoebae was also affected. Based on these results, we could show that CsrA is involved in the regulation of the bacterial switch from the replicative to the transmissible form.     

The yeast Pho80–Pho85 cyclin–CDK complex has multiple substrates

The Pho85–Pho80 cyclin–CDK (cyclin-dependent protein kinase) complex of Saccharomyces cerevisiae functions as a key regulator of the phosphate-repressible acid phosphatase system. We have further characterized the Pho85–Pho80 kinase complex and identified the Pho80 cyclin subunit and the Pho81 CDK inhibitor as substrates of the Pho85 protein kinase. The phosphorylation sites within Pho80 have been identified at Ser²³⁴ and Ser²⁶⁷. Of the two sites, phosphorylation of Ser²³⁴ is required for Pho80 function, to form an active kinase complex and repress acid phosphatase expression. Evidence suggests that the activity of Pho81 is regulated by a post-translational modification and therefore that Pho85-mediated phosphorylation of Pho81 may alter its ability to function as a CDK inhibitor. Thus, the control of acid phosphatase expression involves the phosphorylation of several of the regulatory components of the system.     

Functional characterization of genetic polymorphisms identified in the human cytochrome P450 4F12 (CYP4F12) promoter region

The human cytochrome CYP4F12 has been shown to be active toward inflammatory mediators and exogenous compounds such as antihistaminic drugs. In the present study, we report the first investigation of polymorphisms in the human CYP4F12 gene. A screening for sequence variations in the 5'-flanking region was performed by a Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCR-SSCP) strategy, using DNA samples from 53 unrelated French individuals of Caucasian origin. Several polymorphisms were identified, comprising a large deletion located in intron 1 (CYP4F12*v1), two isolated substitutions -402G>A (CYP4F12*v3) and -188 T>C (CYP4F12*v4) and nine combined mutations, -474T>C, -279A>C, -224A>G, -173G>A, -145C>G, -140T>C, -126T>C, -56T>C, and -21T>G (CYP4F12*v2). Considering the nature and location of the polymorphisms characterizing the CYP4F12*v1 and *v2, the functional relevance of those two allelic variants was further examined by transfecting different cell lines with constructs of the related region of the CYP4F12/luciferase reporter gene. Both alleles lead to a significant decrease of CYP4F12 gene expression in HepG2 cell line and, therefore, are likely to determine interindividual differences in CYP4F12 gene expression.